Description

Telithromycin, sold under the brand name Ketek®, is a semisynthetic antibiotic that belongs to the ketolide class. Ketolides are a novel subclass of macrolide antibiotics. Telithromycin is distinguished by its unique structure, which makes it effective against bacteria that have developed resistance to older macrolide antibiotics like erythromycin. However, due to reports of serious side effects, particularly liver toxicity and the risk of exacerbating myasthenia gravis, its use has become highly restricted.

Indications

Telithromycin’s indications have been significantly narrowed due to safety concerns. Its current and primary approved indication is:

• Community-acquired pneumonia (CAP): It is used for the treatment of mild-to-moderate CAP caused by susceptible strains of bacteria, including multi-drug resistant strains of Streptococcus pneumoniae, which are often resistant to other macrolides.

In many countries, it is contraindicated in patients with myasthenia gravis, and its use is limited to situations where other antibiotics are not suitable.

Mechanism of Action

Telithromycin works by inhibiting bacterial protein synthesis, a process essential for the growth and survival of bacteria. Its mechanism is similar to that of macrolides, but with key differences that make it more potent and effective against resistant strains.

1. Ribosome Binding: Like macrolides, telithromycin works by binding to the 50S ribosomal subunit of the bacterial ribosome. The ribosome is the cellular machinery responsible for translating genetic information into proteins.

2. Dual Binding Sites: A key distinction of telithromycin is its ability to bind simultaneously to two different domains of the 23S ribosomal RNA (rRNA) within the 50S subunit—domains II and V. Older macrolides typically bind strongly to only one of these domains. This dual-binding action gives telithromycin a much higher affinity for the ribosome and makes it more effective against bacteria that have resistance mechanisms affecting a single site.

3. Inhibition of Peptide Synthesis: By binding to these sites, telithromycin prevents the ribosome from elongating the growing polypeptide chain. This blocks protein synthesis, which ultimately stops the bacteria from growing and multiplying.

4. Bactericidal and Bacteriostatic Effect: Telithromycin’s effect can be either bacteriostatic (inhibiting growth) or bactericidal (killing the bacteria) depending on the concentration of the drug.

In addition to its antibacterial action, telithromycin has a unique side-effect mechanism. It has been shown to act as an antagonist on cholinergic receptors in the neuromuscular junction, which is believed to be the cause of the severe respiratory failure reported in some patients with myasthenia gravis.